tbuckley/cabot-search huggingface dataset:
Comparative effectiveness of two- and three-dose COVID-19 vaccination schedules involving AZD1222 and BNT162b2 in people with kidney disease: a linked OpenSAFELY and UK Renal Registry cohort study
Authors: Edward P.K. Parker, Elsie M.F. Horne, William J. Hulme, John Tazare, Bang Zheng, Edward J. Carr, Fiona Loud, Susan Lyon, Viyaasan Mahalingasivam, Brian MacKenna, Amir Mehrkar, Miranda Scanlon, Shalini Santhakumaran, Retha Steenkamp, Ben Goldacre, Jonathan A.C. Sterne, Dorothea Nitsch, Laurie A. Tomlinson
Journal: The Lancet Regional Health - Europe (2023)

Kidney disease is a key risk factor for COVID-19-related mortality and suboptimal vaccine response. Optimising vaccination strategies is essential to reduce the disease burden in this vulnerable population. We therefore compared the effectiveness of two- and three-dose schedules involving AZD1222 (AZ; ChAdOx1-S) and BNT162b2 (BNT) among people with kidney disease in England.
Environmental Exposure to Emerging Alternatives of Per- and Polyfluoroalkyl Substances and Polycystic Ovarian Syndrome in Women Diagnosed with Infertility: A Mixture Analysis
Authors: Wenqiang Zhan, Wei Qiu, Yan Ao, Wei Zhou, Yun Sun, Han Zhao, Jun Zhang
Journal: Environmental Health Perspectives (2023)

Background: Per- and polyfluoroalkyl substances (PFAS) have been previously linked to polycystic ovarian syndrome (PCOS), but only a few legacy PFAS were examined. Objectives: This study aimed to explore this association with a variety of PFAS, including legacy, branched-chain isomers, and emerging alternatives, as well as a PFAS mixture. Methods: From 2014 to 2016, we conducted a multicenter, hospital-based case–control study on environmental endocrine disruptors and infertility in China. Three hundred sixty-six women with PCOS-related infertility and 577 control participants without PCOS were included in the current analysis. Twenty-three PFAS, including 3 emerging PFAS alternatives, 6 linear and branched PFAS isomers, 6 short-chain PFAS, and 8 legacy PFAS, were quantified in the plasma. Logistic regression and two multipollutant models [quantile-based g-computation (QGC) and Bayesian kernel machine regression (BKMR) methods] were used to assess the association of individual PFAS and PFAS mixture with PCOS, as well as the potential interactions among the congeners. Results: After adjusting for potential confounders, Each 1-standard deviation higher difference in ln-transformed 6:2 chlorinated perfluoroalkyl ether sulfonic acid (6:2 Cl-PFESA) and hexafluoropropylene oxide dimer acid (HFPO-DA) level was significantly associated with a 29% (95% CI: 1.11, 1.52) and 39% (95% CI:1.16, 1.68) higher odds of PCOS, respectively. Meanwhile, branched isomers of perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS) (i.e., br-PFHxS, n-PFOS, 1m-PFOS, Σ3,4,5m-PFOS), short-chain PFAS (i.e., PFPeS and PFHxA) and other legacy PFAS [i.e., total concentrations of PFOS (T-PFOS), and perfluorododecanoic acid (PFDoA)] were significantly associated with increased odds of PCOS. The PFAS mixture was positively related to PCOS in the BKMR model. A similar trend was observed in QGC model, a ln-unit increase in the PFAS mixture was associated with a 20% increased risk of PCOS [adjusted odds ratio (aOR)=1.20 (95% CI: 1.06, 1.37)]. After controlling for other PFAS homologs, 6:2 Cl-PFESA, HFPO-DA, Σ3,4,5m-PFOS, and PFDoA were the major contributors based on the QGC and BKMR models. The associations were more pronounced in overweight/obese women. Conclusions: In this group of women, environmental exposure to a PFAS mixture was associated with an elevated odds of PCOS, with 6:2 Cl-PFESA, HFPO-DA, Σ3,4,5m-PFOS, and PFDoA being the major contributors, especially in overweight/obese women. https://doi.org/10.1289/EHP11814
How trivial is lumen-apposing metal stent retrieval?
Authors: Xavier Dray
Journal: Endoscopy (2023)

Lumen-apposing metal stents (LAMSs) were originally conceived for transgastric or transduodenal endoscopic drainage of symptomatic pancreatic pseudocysts and walled-off necrosis (WON). Their inner diameter is large enough to allow direct endoscopic necrosectomy, and their wide flanges on both ends provide an effective anchorage with lower rates of migration. “Hot LAMS” systems are enhanced with an electrocautery tip that allows fast and easy stent delivery, and limits the use of ancillary tools and fluoroscopy. Many off-label indications for LAMSs have emerged, notably for endoscopic ultrasound (EUS)-guided biliary drainage, when endoscopic retrograde cholangiopancreatography fails or is not feasible [1]. Although the US Food and Drug Administration has approved a 60-day maximum stent indwell time, longer and sometimes permanent stent placements are performed, especially in patients with malignant disease. Overall, the decision to retrieve a LAMS and the timing of this should be part of a global strategy.
Differences in <scp>JAK</scp> Isoform Selectivity Among Different Types of <scp>JAK</scp> Inhibitors Evaluated for Rheumatic Diseases Through In Vitro Profiling
Authors: Anniina Virtanen, Maaria Palmroth, Sanna Liukkonen, Antti Kurttila, Teemu Haikarainen, Pia Isomäki, Olli Silvennoinen
Journal: Arthritis & Rheumatology (2023)

The selectivity of JAK inhibitors (Jakinibs) forms the basis for understanding their clinical characteristics; however, evaluation of selectivity is hampered by the lack of comprehensive head-to-head studies. Our objective was to profile in parallel Jakinibs indicated or evaluated for rheumatic diseases for their JAK and cytokine selectivity in vitro.We analyzed 10 Jakinibs for JAK isoform selectivity by assaying their inhibition of JAK kinase activity, binding to kinase and pseudokinase domains, and inhibition of cytokine signaling using blood samples from healthy volunteers and using isolated peripheral blood mononuclear cells (PBMCs) from patients with rheumatoid arthritis and from healthy donors.Pan-Jakinibs effectively suppressed kinase activity of 2 to 3 JAK family members, whereas isoform-targeted Jakinibs possessed varying degrees of selectivity for 1 or 2 JAK family members. In human leukocytes, Jakinibs predominantly inhibited the JAK1-dependent cytokines interleukin-2 (IL-2), IL-6, and interferons (IFNs). In PBMCs from patients with rheumatoid arthritis compared with healthy controls, inhibition of these cytokines was more pronounced, and some cell-type and STAT isoform differences were observed. Novel Jakinibs demonstrated high selectivity: the covalent Jakinib ritlecitinib showed 900- to 2,500-fold selectivity for JAK3 over other JAKs and specific suppression of IL-2-signaling, whereas the allosteric TYK2 inhibitor deucravacitinib inhibited IFNα signaling with high specificity. Interestingly, deucravacitinib targeted the regulatory pseudokinase domain and did not affect JAK in vitro kinase activity.Inhibition of JAK kinase activity did not directly translate into cellular inhibition of JAK/STAT signaling. Despite differences in JAK selectivity, the cytokine inhibition profiles of currently approved Jakinibs were highly similar, with preference for JAK1-mediated cytokines. Novel types of Jakinibs showed narrow cytokine inhibition profile specific for JAK3- or TYK2-mediated signaling.
Abstract 2876: Effectiveness of Band-pass Filter Optimization to Avoid Ventricular Sensing Failure by Novel Implantable Cardioverter Defibrillators
Authors: Daigo Yagishita, Morio Shoda, Tetsuyuki Manaka, Bun Yashiro, Keisuke Futagawa, Koichiro Ejima, Takahiro Sato, Nobuhisa Hagiwara
Journal: Circulation (2009)
Calcific Tendinitis of the Shoulder
Authors: Cathy A. Speed, Brian L. Hazleman
Journal: New England Journal of Medicine (1999)

Calcific tendinitis of the shoulder is a self-limiting calcification of the rotator cuff (Figure 1). Radiologically evident calcification has been reported in 7.5 to 20 percent of adults with no symptoms1,2 and in 6.8 percent of those with shoulder pain.2 The disorder is most common among people between 30 and 60 years of age. Women are slightly more likely to be affected than men, and workers in sedentary jobs appear to be at higher risk than those in manual work. Bilateral involvement is not uncommon.The reason for the deposition of calcium hydroxyapatite crystals in the tendon is unclear. . . .
Predictors of early re-bleeding and mortality after acute variceal haemorrhage in patients with cirrhosis
Authors: K Bambha, W R Kim, R Pedersen, J P Bida, W K Kremers, P S Kamath
Journal: Gut (2008)

<h3>Background and aims:</h3> Risk factors for mortality and re-bleeding following acute variceal haemorrhage (AVH) are incompletely understood. The aim of this study was to determine risk factors for 6-week mortality, and re-bleeding within 5 days in patients with cirrhosis and AVH. <h3>Methods:</h3> Kaplan–Meier and Cox proportional hazards regression analyses were used to determine risk factors among 256 patients with AVH entered into a randomised, prospective trial. <h3>Results:</h3> Thirty-five patients (14%) died within 6 weeks of AVH; 14 deaths (40%) occurred within 5 days. Only the Model for End-stage Liver Disease (MELD) score and units of packed red blood cells (PRBCs) transfused in the first 24 h were associated with 6-week mortality univariately (HR 1.11, p&lt;0.001; HR 1.22, p&lt;0.001) and bivariately (HR MELD = 1.10, p&lt;0.001; HR per unit of PRBCs transfused = 1.15, p = 0.005). Re-bleeding within 5 days occurred in 37 patients (15%); MELD score (p = 0.01) and a clot on a varix (p = 0.05) predicted re-bleeding. Patients with a MELD score ⩾18; both MELD score ⩾18 and ⩾4 units of PRBCs transfused; both MELD score ⩾18 and active bleeding at index endoscopy; and variceal re-bleeding had increased risk of death 6 weeks post-AVH (HR = 7.4, p&lt;0.001; 11.3, p&lt;0.001; 9.9, p&lt;0.001; 10.2, p&lt;0.001 respectively). <h3>Conclusions:</h3> Patients with AVH and MELD score ⩾18, requiring ⩾4 units of PRBCs within the first 24 h or with active bleeding at endoscopy are at increased risk of dying within 6 weeks. MELD score ⩾18 is also a strong predictor of variceal re-bleeding within the first 5 days.
Receptor-Effector Coupling by G Proteins: Implications for Normal and Abnormal Signal Transduction
Authors: ALLEN M. SPIEGEL, ANDREW SHENKER, LEE S. WEINSTEIN
Journal: Endocrine Reviews (1992)

THE ROLE of heterotrimeric guanine nucleotide binding proteins (G proteins) in signal transduction was first covered in Endocrine Reviews in 1981, when three distinct G proteins involved in visual transduction and regulation of cAMP formation were recognized (1). This topic was updated in Endocrine Reviews in 1989 by which time the number of mammalian G proteins identified had doubled, and their roles in regulation of various phospholipases and ion channels had been recognized (2). Barely 3 years later, the number of distinct mammalian G proteins recognized has again doubled, multiple G proteins have been identified in invertebrates, plants, and single-celled eukaryotes, and the number of cellular functions shown to be regulated by G proteins has increased correspondingly. Numerous excellent reviews covering various aspects of this topic have recently appeared (3–9), but given the rapidity of progress in this field, an update in Endocrine Reviews appears timely. This review summarizes recent progress in our understanding of G protein structure, function, and diversity. Particular emphasis is given to the problem of defining specificity in coupling of receptors to various G proteins, and the involvement of abnormal G proteins in human disease. Two related areas, that of G protein-coupled receptors (10) and of low molecular weight GTP-binding proteins such as the ras p21 protooncogenes (7, 11, 12), have also undergone an explosive increase in information. Detailed consideration of the structure, function, and diversity of both of these important classes of protein beyond the scope of this review, but selected areas will covered as they relate to the heterotrimeric G proteins themselves. Our citation of the extensive literature on G proteins is not comprehensive; instead, we have emphasized more recent references, and in some instances directed the reader to recent reviews for more detailed coverage of a particular area.
Polypharmacy in the Aging Patient
Authors: Athanase Benetos, Patrick Rossignol, Antonio Cherubini, Laure Joly, Tomasz Grodzicki, Chakravarthi Rajkumar, Timo E. Strandberg, Mirko Petrovic
Journal: JAMA (2015)

<h3>Importance</h3> Hypertension treatment is beneficial for most hypertensive patients. The benefits for patients who are very old and frail, especially those taking numerous medications, are less certain. <h3>Objective</h3> To provide recommendations for the evaluation and treatment of hypertension among patients aged 80 years and older. <h3>Evidence Acquisition</h3> MEDLINE, PubMed Central, and the Cochrane Database of Systematic Reviews were searched from inception through April 2015, with an emphasis on 2010-2015. Manual cross-referencing of review articles and meta-analyses was also performed to identify randomized controlled trials (RCTs) examining antihypertensive use in octogenarians. The search strategy included the following Medical Subject Headings:<i>hypertension</i>or<i>high blood pressure</i>and<i>trials</i>and<i>oldest old</i>or<i>very old</i>or<i>very elderly</i>. <h3>Findings</h3> Six post hoc analyses of the previously published Hypertension in the Very Elderly Trial (HYVET) met the inclusion criteria. In the only placebo-controlled RCT on hypertension management in patients older than 80 years (HYVET; N = 3845), the treatment was associated with lower total mortality and key cardiovascular end points but the effect on stroke (fatal and nonfatal), which was the primary outcome, failed to reach the significance level (<i>P</i> = .06). Post hoc analyses of HYVET suggested that active hypertension treatment in very elderly patients was beneficial by reducing blood pressure in individuals with white coat hypertension, showed moderate benefits of the active treatment for cognition, a possible effect for fractures prevention, and sustained differences in reductions of total mortality and cardiovascular mortality in those receiving active treatment. However, patients were community dwelling and less disabled than individuals of the same age in general. <h3>Conclusions and Relevance</h3> Hypertensive patients who are healthy, functionally independent, and aged 80 years and older should be treated according to current recommendations for people older than 65 years. There is insufficient evidence regarding the benefits of hypertension treatment for frail polymedicated octogenarians, for whom treatment should be individualized.
A multivariate analysis of risk factors for hepatocellular carcinogenesis: A prospective observation of 795 patients with viral and alcoholic cirrhosis
Authors: Kenji Ikeda, Satoshi Saitoh, Isao Koida, Yasuji Arase, Akihito Tsubota, Kazuaki Chayama, Hiromitus Kumada, Masahiro Kawanishi
Journal: Hepatology (1993)

To elucidate the appearance rates of hepatocellular carcinoma in cirrhosis and to assess the risk factors for hepatocellular carcinogenesis, we prospectively studied 795 consecutive patients with viral or alcoholic cirrhosis for 2 to 17 yr (median of 5.8 yr). During the observation period, hepatocellular carcinoma developed in 221 patients. Cumulative appearance rates of hepatocellular carcinoma were 19.4%, 44.3% and 58.2% at the end of the fifth, tenth and fifteenth years, respectively. When classified by the type of hepatitis virus infection, the appearance rates of hepatocellular carcinoma in 180 patients with only HBsAg and in 349 patients with only antibodies to hepatitis C virus were 14.2% and 21.5% at the fifth yr, 27.2% and 53.2% at the tenth yr and 27.2% and 75.2% at the fifteenth yr, respectively. Cox proportional hazard model identified that α-fetoprotein levels (p = 0.00001), age (p = 0.00067), positive hepatitis C virus antibodies (p = 0.00135), total alcohol intake (p = 0.00455) and indocyanine green retention rate (p = 0.04491) were independently associated with the appearance rates of hepatocellular carcinoma. Whereas age and indocyanine green retention rate were independent predictors for the appearance rate of liver tumor in the subgroup of HBsAg-positive patients, α-fetoprotein levels, age and past alcohol consumption were independent predictors in the group of hepatitis C virus antibody–positive patients. These epidemiological results suggest that some differences exist in the activity and modes of cancer promotion between hepatitis B virus infection and hepatitis C virus infection. (HEPATOLOGY 1993;18:47–53).
Clonidine-Suppression Test
Authors: Emmanuel L. Bravo, Robert C. Tarazi, Fetnat M. Fouad, Donald G. Vidt, Ray W. Gifford
Journal: New England Journal of Medicine (1981)

THE diagnosis of pheochromocytoma is considered secure when typical signs and symptoms (e.g., hypertension, sweating, palpitation, and headaches) are associated with unequivocal biochemical evidence of excessive catecholamine production. However, excluding the diagnosis in the 5 to 10 per cent of patients with essential hypertension who have suggestive symptoms and borderline increases in plasma catecholamines or urinary catecholamine metabolites or both remains a common problem. In such patients, the basic approach is pharmacologic. Pharmacologic agents are administered either to provoke the release of a catecholamine or to block its action. The resulting changes in indexes of catecholamine release or blood pressure . . .
The Value of Maintenance Theophylline in Steroid-Dependent Asthma
Authors: Edward G. Nassif, Miles Weinberger, Robert Thompson, William Huntley
Journal: New England Journal of Medicine (1981)

We examined the value of maintenance theophylline at serum concentrations of 10 to 20 μg per milliliter in a placebo-controlled, randomized, double-blind trial of 33 children with steroid-dependent chronic asthma. Patients were free of all symptoms 63±6 per cent of the days (mean ±S.E.M.) when taking theophylline as compared with 42±6 per cent when taking placebo (P≤0.01). Inhaled metaproterenol was required twice as often with placebo (P≤0.01), and additional daily corticosteroids were needed more than three times as often with placebo (P ≡ 0.02). Daily peak flow measurements improved with theophylline (P≤0.01) as did monthly spirometric measurements and residual volume measured by plethysmography. Theophylline was associated with a 50 per cent increase in the number of patients able to complete an exercise test (P≡0.01) and with a smaller decrease in forced expiratory volume in one second among patients completing the exercise (P≤0.02). We conclude that maintenance bronchodilator therapy with theophylline can provide clinically important benefit for patients with chronic steroid-dependent asthma. (N Engl J Med. 1981; 304:71–5.)
The association of increased levels of intermediate-density lipoproteins with smoking and with coronary artery disease.
Authors: G Steiner, L Schwartz, S Shumak, M Poapst
Journal: Circulation (1987)

Studies were undertaken to determine whether there is an association between elevated levels of intermediate-density lipoproteins (IDL) (Sf 12-60 lipoproteins) and coronary artery disease. Forty-five to sixty-five-year-old men with objectively documented coronary artery disease (n = 58) who were free of known risk factors (diabetes, hypertension, obesity, hyperuricemia, and hypercholesterolemia) were compared with similar men who were free of coronary artery disease (n = 52). Smokers could not be excluded. The coronary artery disease group had a higher rate of cigarette smoking (NS, due to large variations); higher concentrations of triglycerides in their plasma (p = .003) and higher levels of very low-density lipoproteins (VLDL) (p = .007), IDL (p = .016), and low-density lipoproteins (LDL) (p = .04); as well as somewhat lower levels of high-density lipoprotein (HDL) cholesterol (p = .04). Chi-squared analysis demonstrated a strong association between coronary artery disease and IDL apolipoprotein (apo) B (p = .006), coronary artery disease and IDL triglyceride (p = .032), and coronary artery disease and IDL apo B times IDL triglyceride (p = .006) when the top quintile of the population was compared with the bottom quintile for each of these variables. Stepwise logistic regression analysis resulted in rejection of an association between coronary artery disease and HDL cholesterol, plasma triglyceride, VLDL triglyceride, or LDL triglyceride. However, it did show that coronary artery disease was most strongly associated with smoking and that the second strongest association was with IDL.(ABSTRACT TRUNCATED AT 250 WORDS)
Diagnostic Value of Liver Non-Contrast Perfusion in Prediction of Visceropathies (Sialadenitis and Hepatic Encephalopathy) in Patients with Diffuse Liver Diseases
Authors: A. A. Telesh, T. G. Morozova, A. A. Tarasov, V. G. Morozov
Journal: Radiology - Practice (2023)

The aim of this work is to evaluate diagnostic value of liver non-contrast perfusion in prediction of visceropathies (sialadenitis and hepatic encephalopathy) in patients with diffuse liver diseases (DLD). Clinical and laboratory data (including the Raitan test), results of MRI with non-contrast MR perfusion (ASL-perfusion) of the liver and brain MRI with assessment of the head and neck soft tissues were estimated in a group of patients with DLD. Potentials of assessment of ASL liver perfusion for hepatic encephalopathy and sialadenitis prediction are described in the article. Based on the clinical and laboratory data and results of histopathological analysis of salivary gland biopsies, it was established that sialadenitis in patients with DLD is the result of disturbance of macroorganism resistance; sialadenitis in this context is the inflammatory process of the gland with acinuses atrophy signs, in MRI it forms pictures of the gland enlargement without visible macrostructure changes. The study showed that the integrated approach to observation of patients with DLD (radiologist + gastroenterologist / infectious disease specialist + otorhinolaryngologist / dentist) helps correct of patient monitoring tactics timely and effective.
Possibilities of Magnetic Resonance Imaging in the Diagnosis of Ductal Adenocarcinoma of the Prostate (Clinical Case)
Authors: D. Kh. Khamidov, N. A. Rubtsova, A. Yu. Elhova, A. V. Levshakova, A. A. Krasheninnikov, B. Ya. Alekseev, A. D. Kaprin
Journal: Radiology - Practice (2023)

This article presents a clinical case demonstrating the possibilities of MRI of the pelvic under the assumption of a histological variant of a prostate tumor. The main MR-patterns of the ductal adenocarcinoma, as well as the variants of their occurrence are considered. The authors present an analysis of data of differential diagnosis of various histological variants of prostate cancer.